EP2323502A1 - Flavan-3-ol containing foodstuffs - Google Patents

Flavan-3-ol containing foodstuffs

Info

Publication number
EP2323502A1
EP2323502A1 EP09781348A EP09781348A EP2323502A1 EP 2323502 A1 EP2323502 A1 EP 2323502A1 EP 09781348 A EP09781348 A EP 09781348A EP 09781348 A EP09781348 A EP 09781348A EP 2323502 A1 EP2323502 A1 EP 2323502A1
Authority
EP
European Patent Office
Prior art keywords
acid
flavan
ols
compound
propanoic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP09781348A
Other languages
German (de)
French (fr)
Other versions
EP2323502B1 (en
Inventor
Robertus Johannes Gouka
Afrodite Lourbakos
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Unilever PLC
Unilever NV
Original Assignee
Unilever PLC
Unilever NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Unilever PLC, Unilever NV filed Critical Unilever PLC
Priority to PL09781348T priority Critical patent/PL2323502T3/en
Priority to EP09781348A priority patent/EP2323502B1/en
Publication of EP2323502A1 publication Critical patent/EP2323502A1/en
Application granted granted Critical
Publication of EP2323502B1 publication Critical patent/EP2323502B1/en
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23F—COFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
    • A23F3/00—Tea; Tea substitutes; Preparations thereof
    • A23F3/40—Tea flavour; Tea oil; Flavouring of tea or tea extract
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23F—COFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
    • A23F3/00—Tea; Tea substitutes; Preparations thereof
    • A23F3/06—Treating tea before extraction; Preparations produced thereby
    • A23F3/14—Tea preparations, e.g. using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23F—COFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
    • A23F3/00—Tea; Tea substitutes; Preparations thereof
    • A23F3/16—Tea extraction; Tea extracts; Treating tea extract; Making instant tea
    • A23F3/163—Liquid or semi-liquid tea extract preparations, e.g. gels or liquid extracts in solid capsules
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/204—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/86—Addition of bitterness inhibitors
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives

Definitions

  • the present invention is directed to compounds and compositions for the reduction or elimination of bitterness caused by flavan-3-ols.
  • tea is the most popular beverage consumed by man. Tea is very refreshing, can be served either hot or cold, and has been made commercially available for many years. Lipton®, for example, is the world's leading brand of tea, made available in over 1 10 countries by Unilever.
  • tea which has a unique combination of natural antioxidants known as flavonoids that can include flavan-3-ols, flavonols and flavonol glucosides.
  • flavonoids can include flavan-3-ols, flavonols and flavonol glucosides.
  • tea can help improve vascular function, combat fatigue, reduce cholesterol levels and increase feelings of vitality.
  • flavan-3-ols such as catechins
  • the flavan-3-ols found in tea have many health benefits and epigallocatechin gallate, epicatechin, epicatechin gallate, and epigallocatechin have been shown to positively impact physiological activities, and their use as antiallergic agents and cerebral function activators has been proposed.
  • flavan-3-ols In view of the many positive contributions associated with flavan-3-ols, it is desirable to formulate consumable compositions, such as beverages and food, with elevated levels of flavan-3-ols. Unfortunately, increased amounts of flavan-3-ols can lead to end use products that can have poor organoleptic properties, in particular bitter taste.
  • US 2003/0096050 discloses a food composition containing catechins (i.e. flavan-3-ols) and gallic acid wherein the gallic acid is alleged to have a certain bitterness mitigating effect. There is therefore a need for consumable compositions with elevated levels of flavan-3-ols with improved bitterness reduction.
  • flavan-3-ols is used as a generic term for catechins, theaflavins, thearubigins, and mixtures thereof.
  • catech i ns As used herein the term "catech i ns" is used as a generic term for catech i n, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, and mixtures thereof.
  • the term "theaflavins" is used as a generic term for theaflavi n, isotheaflavin, neotheaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'- digallate, epitheaflavic acid, epitheaflavic acid-3'-gallate, theaflavic acid, theaflavic acid-3'-gallate and mixtures thereof.
  • the structures of these compounds are well- known (see, for example, structures xi-xx in Chapter 17 of "Tea - Cultivation to consumption", K. C. Willson and M.N.
  • theaflavins includes salt forms of these compounds.
  • the preferred theaflavins are theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'-digallate and mixtures thereof, as these theaflavins are most abundant in natural sources, such as black tea.
  • the term "beverage” refers to a substantially aqueous drinkable composition suitable for human consumption.
  • the beverage comprises at least 85% water by weight of the beverage, more preferably at least 90% and most preferably from 95 to 99.9%.
  • Tea solids refers to dry material extractable from the leaves of the plant Camellia sinensis var. sinensis and/or Camellia sinensis var. assamica.
  • the material may have been subjected to a so-called “fermentation” step wherein it is oxidised by certain endogenous enzymes that are released during the early stages of "black tea” manufacture. This oxidation may even be supplemented by the action of exogenous enzymes such as oxidases, laccases and peroxidases.
  • the materia l may have been pa rtia l ly fermented ("oolong " tea) o r su bsta ntia l ly unfermented ("green tea”).
  • tea-based beverage refers to a beverage comprising at least 0.01% by weight tea solids.
  • tea-based beverage comprises from 0.04 to 3% by weight tea solids, more preferably from 0.06 to 2%, most preferably from 0.1 to 1%.
  • the term “elevated levels of flavan-3-ols” refers to compositions comprising at least 0.01 wt% flavan-3-ols.
  • the term "effective amount" refers to at least 0.01 wt% of the compound or compounds for the reduction or elimination of bitterness caused by flavan-3-ols.
  • the present invention provides the use of a compound of formula (I):
  • R 1 represents C 2 - C 3 saturated or unsaturated divalent hydrocarbon radical, n is an integer from 0 to 3, and each X is independently selected from C 1 - C 3 alkyloxy and OH; and wherein if n is 0 then R 1 is C 3 saturated divalent hydrocarbon radical or C 2 - C 3 unsaturated divalent hydrocarbon radical; and wherein if n is greater than 0 then the compound has formula (II)
  • the present invention provides a composition comprising greater than 0.01 wt % flavan-3-ols and an effective amount of at least one compound of formula (I).
  • An advantage of this aspect of the present invention is that such a composition will allow consumers to reach the required intake of flavan-3-ols with fewer servings of, for example, a high-flavan-3-ol tea without the aversive effects of enhanced bitterness that this would normally introduce.
  • the present invention provides a method of manufacturing the composition, the method comprising the steps of: providing a first substance comprising flavan-3-ols and a second substance comprising the at least one compound of formula (I), combining the two substances, and recovering the composition.
  • the present invention provides a method for the reduction or elimination of bitterness caused by flavan-3-ols comprising consuming a first substance and a second substance, simultaneously or sequentially, wherein the first substance comprises flavan-3-ols and the second substance comprises an effective amount of at least one compound of formula (I).
  • the present invention is directed to consumable compositions that contain high levels of flavan-3-ols in which the bitter taste of the flavan-3-ols is reduced.
  • the present invention provides for the use of a compound of formula (I) that is more effective at blocking flavan-3-ol bitterness.
  • the compound is particularly effective at blocking the bitter taste of catechins and hence a preferred use is for blocking bitterness caused by catechins.
  • Especially effective, and thus preferred compounds are those wherein each X of formula (I) is independently selected from methoxy and OH.
  • preferred compounds are those wherein if n of formula (I) is 0 then R 1 is C 2 unsaturated divalent hydrocarbon radical or C 3 saturated divalent hydrocarbon radical.
  • Particularly preferred compounds are: Cinnamic acid,
  • the present invention also provides for a composition
  • a composition comprising greater than 0.01 wt% flavan-3-ols, preferably greater than 0.02 wt% flavan-3-ols, more preferably greater than 0.05 wt% flavan-3-ols and an effective amount of at least one compound of formula (I).
  • the flavan-3-ols are one or more catechins.
  • the amount of the compound is typically at least 0.05 wt%, more preferably at least 0.075 wt%, most preferably at least 0.1 wt%.
  • the amount of the compound is typically at most 1.5 wt%, more preferably at most 0.75 wt%, most preferably at most 0.25 wt%.
  • the preferred form of the composition is a food, more preferably a beverage, most preferably a tea- based beverage.
  • the compound is one or more of: Cinnamic acid, 4- Phenylbutanoic acid, 3-(3,4,5-tri methoxyphenyl) pro pa noic acid, 3,4, 5- trimethoxycinnamic acid, 3-(4-methoxyphenyl)propanoic acid, 4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl)propanoic acid, 3,4- dimethoxycinnamic acid, 4-hydroxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid, 3,4-dihydroxycinnamic acid, 3-(3-methoxy-4-hydroxyphenyl)propanoic acid, 3- methoxy-4-hydroxycinnamic acid, and 4-hydroxy-3,5-dimethoxycinnamic
  • the com pou nd is one or more of: 4-Phenylbutanoic acid, 3-(3,4,5- tri methoxyphenyl) propa noic acid, 3,4, 5-trimethoxycinnamic acid, 3-(4- methoxyphenyOpropanoic acid, 4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl) propa noic acid, 3,4-dimethoxycinnamic acid, 3-(3,4- dihydroxyphenyl)propanoic acid, and 3-(3-methoxy-4-hydroxyphenyl)propanoic acid.
  • the present invention further provides a method of manufacturing the composition, the method comprising the steps of: providing a first substance comprising flavan-3- ols and a second substance comprising the at least one compound of formula (I), combining the two substances, and recovering the composition.
  • the first substance comprises catechins.
  • the present invention finally provides a method for the reduction or elimination of bitterness caused by flavan-3-ols comprising consuming a first substance and a second substance wherein the first substance comprises flavan-3-ols and the second substance comprises an effective amount of at least one compound of formula (I).
  • the first substance comprises catechins.
  • the first and second substances are consumed simultaneously as part of the same meal, more preferably the first and second substances a re consumed si m ulta neously i n the sa me com position .
  • the first and second substances are consumed sequentially, most preferably when consumed sequentially, the first substance is consumed after the second substance.
  • TAS2R39 Activation of the bitter receptor TAS2R39 causes the release of calcium from the endoplasmic reticulum of those cells containing the receptor. Therefore, changes in calcium levels within cells expressing TAS2R39 serves as a proxy marker for the activity of the receptor.
  • An assay was used to assess the stimulation of TAS2R39 by the flavan- 3-ol epicatechin gallate (ECG) and to assess the inhibition of this stimulation of TAS2R39 through the use of various compounds as follows:
  • HEK293 cells expressing the human bitter receptor TAS2R39 and a G-protein that allows coupling to a calcium readout system were maintained in Dulbecco's Modified Eagle's Medium (DMEM) containing DMEM and 10% tetracycline-free fetal bovine serum (Cambrex) supplemented with blasticidin (5 ⁇ g/ml) geneticin (400 ⁇ g/ml) and hygromycin (100 ⁇ g/ml). Cells were grown and maintained at 37°C / 5% CO 2 .
  • DMEM Dulbecco's Modified Eagle's Medium
  • blasticidin 5 ⁇ g/ml
  • geneticin 400 ⁇ g/ml
  • hygromycin 100 ⁇ g/ml
  • Intracellular calcium levels were monitored using a Flexstation Il 384.
  • the 96-well plate was loaded onto the Flexstation Il 384 and fluorescence measurements were carried out at 37°C at an excitation wavelength of 485nm and an emission wavelength of 520nm.
  • Activity of TAS2R39 was measured as the change in fluorescence ( ⁇ F) which was calculated by subtracting the maximum fluorescence after the addition of the test or comparative solution from the baseline fluorescence measured before addition of the test or comparative solution.
  • TAS2R39 activity was measured as the percentage reduction of ⁇ F in the presence of ECG alone, compared to ⁇ F in the presence of ECG plus a test compound.
  • the test compounds, their structures and the percentage inhibition of TAS2R39 activity is given in the following table. 3,4,5-trihydroxybenzoic acid (gallic acid) was included in the selection of the test compounds.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Dispersion Chemistry (AREA)
  • Non-Alcoholic Beverages (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Seasonings (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Tea And Coffee (AREA)
  • General Preparation And Processing Of Foods (AREA)

Abstract

The use of a compound for the reduction or elimination of bitterness caused by flavan- 3-ols is provided. Compositions having greater than 0.01 wt % flavan-3-ols and that comprise an effective amount of the com pound are also provided. The compound conforms to the eneral formula (I) wherein R1 represents C2 - C3 saturated or unsaturated divalent hydrocarbon radical, n is an integer from 0 to 3, and each X is independently selected from C1 - C3 alkyloxy and OH; and wherein if n is 0 then R1 is C3 saturated divalent hydrocarbon radical or C2 - C3 unsaturated divalent hydrocarbon radical; and wherein if n is greater than 0 then the compound has formula (II).

Description

Flavan-3-ol Containing Foodstuffs
Technical field of the invention
The present invention is directed to compounds and compositions for the reduction or elimination of bitterness caused by flavan-3-ols.
Background to the invention
Excluding water, tea is the most popular beverage consumed by man. Tea is very refreshing, can be served either hot or cold, and has been made commercially available for many years. Lipton®, for example, is the world's leading brand of tea, made available in over 1 10 countries by Unilever.
Today, modern scientists are exploring the exciting potential of tea, which has a unique combination of natural antioxidants known as flavonoids that can include flavan-3-ols, flavonols and flavonol glucosides. Taken regularly, tea can help improve vascular function, combat fatigue, reduce cholesterol levels and increase feelings of vitality.
Studies have found that the flavan-3-ols, such as catechins, found in tea have many health benefits and epigallocatechin gallate, epicatechin, epicatechin gallate, and epigallocatechin have been shown to positively impact physiological activities, and their use as antiallergic agents and cerebral function activators has been proposed.
In view of the many positive contributions associated with flavan-3-ols, it is desirable to formulate consumable compositions, such as beverages and food, with elevated levels of flavan-3-ols. Unfortunately, increased amounts of flavan-3-ols can lead to end use products that can have poor organoleptic properties, in particular bitter taste.
US 2003/0096050 discloses a food composition containing catechins (i.e. flavan-3-ols) and gallic acid wherein the gallic acid is alleged to have a certain bitterness mitigating effect. There is therefore a need for consumable compositions with elevated levels of flavan-3-ols with improved bitterness reduction. Definitions
Flavan-3-ols
As used herein the term "flavan-3-ols" is used as a generic term for catechins, theaflavins, thearubigins, and mixtures thereof.
Catechins
As used herei n the term "catech i ns" is used as a generic term for catech i n, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, and mixtures thereof.
Theaflavins
As used herein the term "theaflavins" is used as a generic term for theaflavi n, isotheaflavin, neotheaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'- digallate, epitheaflavic acid, epitheaflavic acid-3'-gallate, theaflavic acid, theaflavic acid-3'-gallate and mixtures thereof. The structures of these compounds are well- known (see, for example, structures xi-xx in Chapter 17 of "Tea - Cultivation to consumption", K. C. Willson and M.N. Clifford (Eds), 1992, Chapman & Hall, London, pp.555-601 ). The term theaflavins includes salt forms of these compounds. The preferred theaflavins are theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'-digallate and mixtures thereof, as these theaflavins are most abundant in natural sources, such as black tea.
Beverage
As used herein the term "beverage" refers to a substantially aqueous drinkable composition suitable for human consumption. Preferably the beverage comprises at least 85% water by weight of the beverage, more preferably at least 90% and most preferably from 95 to 99.9%.
Tea solids As used herein, the term "tea solids" refers to dry material extractable from the leaves of the plant Camellia sinensis var. sinensis and/or Camellia sinensis var. assamica. The material may have been subjected to a so-called "fermentation" step wherein it is oxidised by certain endogenous enzymes that are released during the early stages of "black tea" manufacture. This oxidation may even be supplemented by the action of exogenous enzymes such as oxidases, laccases and peroxidases. Alternatively the materia l may have been pa rtia l ly fermented ("oolong " tea) o r su bsta ntia l ly unfermented ("green tea").
Tea-based beverage
As used herein, the term "tea-based beverage" refers to a beverage comprising at least 0.01% by weight tea solids. Preferably the tea-based beverage comprises from 0.04 to 3% by weight tea solids, more preferably from 0.06 to 2%, most preferably from 0.1 to 1%.
Elevated levels of flavan-3-ols
As used herein, the term "elevated levels of flavan-3-ols" refers to compositions comprising at least 0.01 wt% flavan-3-ols.
Effective amount
As used herei n, the term "effective amount" refers to at least 0.01 wt% of the compound or compounds for the reduction or elimination of bitterness caused by flavan-3-ols.
Comprising
The term "comprising" is mea nt not to be l im iting to any subsequently stated elements but rather to encompass non-specified elements of major or minor functional importance. In other words the listed steps, elements or options need not be exhaustive. Whenever the words "including" or "having" are used, these terms are meant to be equivalent to "comprising" as defined above.
Brief description of the invention
We have now found that bitterness in consumable compositions with elevated levels of flavan-3-ols may be el i m i nated th rough the use of pa rticu la r com pounds. Accordingly, in a first aspect, the present invention provides the use of a compound of formula (I):
(I)
for the reduction or elimination of bitterness caused by flavan-3-ols, wherein
R1 represents C2 - C3 saturated or unsaturated divalent hydrocarbon radical, n is an integer from 0 to 3, and each X is independently selected from C1 - C3 alkyloxy and OH; and wherein if n is 0 then R1 is C3 saturated divalent hydrocarbon radical or C2 - C3 unsaturated divalent hydrocarbon radical; and wherein if n is greater than 0 then the compound has formula (II)
(II).
We have conducted extensive research into the physiological origin of bitterness from flavan-3-ols. The human tongue perceives bitterness via a family of about 25 related receptors, each of which detects a different set of bitter tasting molecules. Without wishing to be bound by theory, we believe that the bitter taste of flavan-3-ols is caused by the activation of a specific receptor, TAS2R39, by flavan-3-ols. Furthermore, we have found that compounds of formula (I) specifically bind to receptor TAS2R39 and antagonise its activation. Hence compounds according to the invention block or reduce the activation of receptor TAS2R39 by flavan-3-ols and the bitter taste of the flavan-3-ols is alleviated. More specifically, compounds according to formula (I) are more effective at blocking TAS2R39 than gallic acid.
In a second aspect, the present invention provides a composition comprising greater than 0.01 wt % flavan-3-ols and an effective amount of at least one compound of formula (I). An advantage of this aspect of the present invention is that such a composition will allow consumers to reach the required intake of flavan-3-ols with fewer servings of, for example, a high-flavan-3-ol tea without the aversive effects of enhanced bitterness that this would normally introduce.
In a third aspect, the present invention provides a method of manufacturing the composition, the method comprising the steps of: providing a first substance comprising flavan-3-ols and a second substance comprising the at least one compound of formula (I), combining the two substances, and recovering the composition.
In a final aspect, the present invention provides a method for the reduction or elimination of bitterness caused by flavan-3-ols comprising consuming a first substance and a second substance, simultaneously or sequentially, wherein the first substance comprises flavan-3-ols and the second substance comprises an effective amount of at least one compound of formula (I).
Detailed description of the invention
The present invention is directed to consumable compositions that contain high levels of flavan-3-ols in which the bitter taste of the flavan-3-ols is reduced.
The present invention provides for the use of a compound of formula (I) that is more effective at blocking flavan-3-ol bitterness. The compound is particularly effective at blocking the bitter taste of catechins and hence a preferred use is for blocking bitterness caused by catechins. Especially effective, and thus preferred compounds, are those wherein each X of formula (I) is independently selected from methoxy and OH. Alternatively preferred compounds are those wherein if n of formula (I) is 0 then R1 is C2 unsaturated divalent hydrocarbon radical or C3 saturated divalent hydrocarbon radical. Particularly preferred compounds are: Cinnamic acid,
4-Phenylbutanoic acid,
3-(3,4,5-trimethoxyphenyl) propanoic acid,
3,4,5-trimethoxycinnamic acid, 3-(4-methoxyphenyl)propanoic acid,
4-methoxycinnamic acid,
2,4-dimethoxycinnamic acid,
3-(3,4-dimethoxyphenyl)propanoic acid,
3,4-dimethoxycinnamic acid, 4-hydroxycinnamic acid,
3-(3,4-dihydroxyphenyl)propanoic acid,
3,4-dihydroxycinnamic acid,
3-(3-methoxy-4-hydroxyphenyl)propanoic acid,
3-methoxy-4-hydroxycinnamic acid, 4-hydroxy-3,5-dimethoxycinnamic acid, and mixtures thereof.
Yet more preferred compounds are:
4-Phenylbutanoic acid, 3-(3,4,5-trimethoxyphenyl)propanoic acid,
3,4,5-trimethoxycinnamic acid,
3-(4-methoxyphenyl)propanoic acid,
4-methoxycinnamic acid,
2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl)propanoic acid,
3,4-dimethoxycinnamic acid,
3-(3,4-dihydroxyphenyl) propanoic acid,
3-(3-methoxy-4-hydroxyphenyl)propanoic acid, and mixtures thereof.
The present invention also provides for a composition comprising greater than 0.01 wt% flavan-3-ols, preferably greater than 0.02 wt% flavan-3-ols, more preferably greater than 0.05 wt% flavan-3-ols and an effective amount of at least one compound of formula (I). Preferably, the flavan-3-ols are one or more catechins. The amount of the compound is typically at least 0.05 wt%, more preferably at least 0.075 wt%, most preferably at least 0.1 wt%. The amount of the compound is typically at most 1.5 wt%, more preferably at most 0.75 wt%, most preferably at most 0.25 wt%. The preferred form of the composition is a food, more preferably a beverage, most preferably a tea- based beverage. Preferably the compound is one or more of: Cinnamic acid, 4- Phenylbutanoic acid, 3-(3,4,5-tri methoxyphenyl) pro pa noic acid, 3,4, 5- trimethoxycinnamic acid, 3-(4-methoxyphenyl)propanoic acid, 4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl)propanoic acid, 3,4- dimethoxycinnamic acid, 4-hydroxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid, 3,4-dihydroxycinnamic acid, 3-(3-methoxy-4-hydroxyphenyl)propanoic acid, 3- methoxy-4-hydroxycinnamic acid, and 4-hydroxy-3,5-dimethoxycinnamic acid. More prefera bly the com pou nd is one or more of: 4-Phenylbutanoic acid, 3-(3,4,5- tri methoxyphenyl) propa noic acid, 3,4, 5-trimethoxycinnamic acid, 3-(4- methoxyphenyOpropanoic acid, 4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl) propa noic acid, 3,4-dimethoxycinnamic acid, 3-(3,4- dihydroxyphenyl)propanoic acid, and 3-(3-methoxy-4-hydroxyphenyl)propanoic acid.
The present invention further provides a method of manufacturing the composition, the method comprising the steps of: providing a first substance comprising flavan-3- ols and a second substance comprising the at least one compound of formula (I), combining the two substances, and recovering the composition. Preferably, the first substance comprises catechins.
The present invention finally provides a method for the reduction or elimination of bitterness caused by flavan-3-ols comprising consuming a first substance and a second substance wherein the first substance comprises flavan-3-ols and the second substance comprises an effective amount of at least one compound of formula (I). Preferably, the first substance comprises catechins. Preferably the first and second substances are consumed simultaneously as part of the same meal, more preferably the first and second substances a re consumed si m ulta neously i n the sa me com position . Alternatively the first and second substances are consumed sequentially, most preferably when consumed sequentially, the first substance is consumed after the second substance.
Example 1 Evaluation of TSA2R39 inhibitors
Activation of the bitter receptor TAS2R39 causes the release of calcium from the endoplasmic reticulum of those cells containing the receptor. Therefore, changes in calcium levels within cells expressing TAS2R39 serves as a proxy marker for the activity of the receptor. An assay was used to assess the stimulation of TAS2R39 by the flavan- 3-ol epicatechin gallate (ECG) and to assess the inhibition of this stimulation of TAS2R39 through the use of various compounds as follows:
HEK293 cells expressing the human bitter receptor TAS2R39 and a G-protein that allows coupling to a calcium readout system were maintained in Dulbecco's Modified Eagle's Medium (DMEM) containing DMEM and 10% tetracycline-free fetal bovine serum (Cambrex) supplemented with blasticidin (5 μg/ml) geneticin (400 μg/ml) and hygromycin (100 μg/ml). Cells were grown and maintained at 37°C / 5% CO2.
Cells were cultured in a 75 cm2 flask, harvested by trypsinisation and resuspended in DMEM medium. 100 μl of cells per well were added to a poly-L-lysine coated μClear 96- well plate, and incubated overnight. Expression of the TAS2R39 gene was then induced by the addition of 100 μl DM EM medium containing 0.5 μg/ml doxycyclin. After another 24-30 hrs the medium was removed and the cells were loaded for 1 hour with 50 μl Tyrodes buffer (140 mM NaCI, 5 mM KCI, 10 mM glucose, 1 mM CaCI2. 2 H2O, 1 mM MgCI2. 6 H2O, 20 mM HEPES pH 7.4 (Sigma P8761)) containing 2.5 μM of the fluorescent marker of calcium, Fluo-4-AM, followed by a 1-hr incubation at 37°C. The cells were then washed with Tyrodes buffer and finally taken up in 100 μl Tyrodes buffer.
Test solutions containing 0.5mM ECG and 1OmM of the test compounds, dissolved in Tyrodes buffer, were prepared and 100 μl of each test solution was added to the wells of the 96-well plate containing the cells. A comparative solution containing only 0.5mM ECG dissolved in Tyrodes buffer was also prepared and 100 μl was added to a well of the 96-well plate containing the cells.
Intracellular calcium levels were monitored using a Flexstation Il 384. The 96-well plate was loaded onto the Flexstation Il 384 and fluorescence measurements were carried out at 37°C at an excitation wavelength of 485nm and an emission wavelength of 520nm. Activity of TAS2R39 was measured as the change in fluorescence (ΔF) which was calculated by subtracting the maximum fluorescence after the addition of the test or comparative solution from the baseline fluorescence measured before addition of the test or comparative solution.
Inhibition of TAS2R39 activity was measured as the percentage reduction of ΔF in the presence of ECG alone, compared to ΔF in the presence of ECG plus a test compound. The test compounds, their structures and the percentage inhibition of TAS2R39 activity is given in the following table. 3,4,5-trihydroxybenzoic acid (gallic acid) was included in the selection of the test compounds.
Table 1 - Inhibition of TAS2R39 activity
It can clearly be seen that although the test compounds share similar basic moieties, their ability to inhibit the bitter receptor TAS2R39 is varied. Only those compounds according to formula (I) are better than gallic acid. In particular, the results above demonstrate that compounds according to formula I, such as Cinnam ic acid, 4- Phenylb u t a n o i c a c i d , 3-(3,4,5-trimethoxyphenyl)propanoic acid, 3,4,5- trimethoxycinnamic acid, 3-(4-methoxyphenyl)propanoic acid, 4-methoxycinnamic acid, 2,4-d imethoxyci nna mic acid, 3-(3,4-dimethoxyphenyl)propanoic acid, 3,4- dimethoxycinnamic acid, 4-hydroxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid, 3,4-dihydroxycinnamic acid, 3-(3-methoxy-4-hydroxyphenyl)propanoic acid, 3- methoxy-4-hydroxycinnamic acid and 4-hydroxy-3,5-dimethoxycinnamic acid, are more effective inhibitors of TAS2R39 than gallic acid.

Claims

Claims
1. Use of a compound of formula (I):
(I)
for the reduction or elimination of bitterness caused by flavan-3-ols, wherein
R1 represents C2 - C3 saturated or unsaturated divalent hydrocarbon radical, n is an integer from 0 to 3, and each X is independently selected from C1 - C3 alkyloxy and OH; and wherein if n is 0 then R1 is C3 saturated divalent hydrocarbon radical or C2
C3 unsaturated divalent hydrocarbon radical ; and wherein if n is greater than 0 then the compound has formula (II)
(II).
Use according to claim 1 wherein the bitterness is caused by catechins.
3. Use according to claim 1 or claim 2 wherein each X is independently selected from methoxy and OH.
4. Use according to claim 1 or claim 2 wherein if n is 0 then R1 is C2 unsaturated divalent hydrocarbon radical or C3 saturated divalent hydrocarbon radical.
5. Use according to any of the preceding claims wherein the compound is one or more of:
Cinnamic acid, 4-Phenylbutanoic acid,
3-(3,4,5-trimethoxyphenyl)propanoic acid,
3,4,5-trimethoxycinnamic acid,
3-(4-methoxyphenyl)propanoic acid,
4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid,
3-(3,4-dimethoxyphenyl)propanoic acid,
3,4-dimethoxycinnamic acid,
4-hydroxycinnamic acid,
3-(3,4-dihydroxyphenyl)propanoic acid, 3,4-dihydroxycinnamic acid,
3-(3-methoxy-4-hydroxyphenyl)propanoic acid,
3-methoxy-4-hydroxycinnamic acid, and
4-hydroxy-3,5-dimethoxycinnamic acid.
6. Use according to any of the preceding claims wherein the compound is one or more of:
4-Phenylbutanoic acid,
3-(3,4,5-trimethoxyphenyl)propanoic acid,
3,4,5-trimethoxycinnamic acid, 3-(4-methoxyphenyl)propanoic acid,
4-methoxycinnamic acid,
2,4-dimethoxycinnamic acid,
3-(3,4-dimethoxyphenyl)propanoic acid, 3,4-dimethoxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid, and 3-(3-methoxy-4-hydroxyphenyl)propanoic acid.
7. A composition comprising greater than 0.01 wt % flavan-3-ols and an effective amount of at least one compound of formula (I).
8. A composition according to claim 7 wherein the at least one compound is one or more of: Cinnamic acid,
4-Phenylbutanoic acid,
3-(3,4,5-trimethoxyphenyl)propanoic acid,
3,4,5-trimethoxycinnamic acid,
3-(4-methoxyphenyl)propanoic acid, 4-methoxycinnamic acid,
2,4-dimethoxycinnamic acid,
3-(3,4-dimethoxyphenyl)propanoic acid,
3,4-dimethoxycinnamic acid,
4-hydroxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid,
3,4-dihydroxycinnamic acid,
3-(3-methoxy-4-hydroxyphenyl)propanoic acid,
3-methoxy-4-hydroxycinnamic acid, and
4-hydroxy-3,5-dimethoxycinnamic acid.
9. A composition according to claim 7 or claim 8 wherein the at least one compound is one or more of:
4-Phenylbutanoic acid, 3-(3,4,5-trimethoxyphenyl)propanoic acid, 3,4,5-trimethoxycinnamic acid,
3-(4-methoxyphenyl)propanoic acid, 4-methoxycinnamic acid, 2,4-dimethoxycinnamic acid, 3-(3,4-dimethoxyphenyl)propanoic acid, 3,4-dimethoxycinnamic acid, 3-(3,4-dihydroxyphenyl)propanoic acid, and 3-(3-methoxy-4-hydroxyphenyl) propanoic acid.
10. A composition according to any of claims 7 to 9 comprising at least 0.05 wt % flavan-3-ols.
11. A composition according to any of claims 7 to 10 wherein the flavan-3-ols are one or more catechins.
12. A composition according to any one of claims 7 to 1 1 wherein the amount of the at least one compound of formula (I) is from 0.05 to 1.5 wt%.
13. A composition according to any one of claims 7 to 12 wherein the composition is a beverage, preferably a tea-based beverage.
14. A method of manufacturing a composition according to any one of claims 7 to 13, the method comprising the steps of: providing a first substance comprising flavan-3-ols and a second substance comprising the at least one compound of formula (I), combining the two substances, and recovering the composition.
15. A method according to claim 14 wherein the first substance comprises one or more catechins.
16. A method for the reduction or elimination of bitterness caused by flavan-3-ols comprising consuming a first substance and a second substance, simultaneously or sequentially, wherein the first substance comprises flavan-3-ols and the second substance comprises an effective amount of at least one compound of formula (I).
17. A method according to claim 16 wherein the first substance comprises one or more catechins.
EP09781348A 2008-09-05 2009-07-31 Flavan-3-ol containing foodstuffs Not-in-force EP2323502B1 (en)

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Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5634843B2 (en) * 2010-12-10 2014-12-03 花王株式会社 Bitter taste inhibitor
EP2559346B1 (en) * 2011-08-15 2014-03-26 Symrise AG Oleanene-type triterpene glycosides as masking agents
WO2013023942A1 (en) 2011-08-15 2013-02-21 Unilever Plc Food compositions comprising flavan-3-ols
JP5947062B2 (en) * 2012-02-29 2016-07-06 株式会社コーセー Cell growth promoter, collagen production promoter, and anti-wrinkle agent
MX370090B (en) 2013-02-01 2019-10-25 Centro De Investig En Alimentacion Y Desarrollo A C Method and system for the integral treatment of wastewater from the maize industry.
JP7807049B2 (en) * 2022-02-16 2026-01-27 丸善製薬株式会社 Beverage, taste enhancer, and taste enhancing method
JP7808322B2 (en) * 2022-02-16 2026-01-29 丸善製薬株式会社 Beverage, taste enhancer, and taste enhancing method
CN118266572A (en) * 2024-02-26 2024-07-02 华南理工大学 Application of 3-methoxyphenyl-2-acrylic compound as bitter taste inhibitor

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US533613A (en) * 1895-02-05 S peters co
US5232735A (en) * 1990-06-01 1993-08-03 Bioresearch, Inc. Ingestibles containing substantially tasteless sweetness inhibitors as bitter taste reducers or substantially tasteless bitter inhibitors as sweet taste reducers
US5336513A (en) * 1991-02-20 1994-08-09 Kraft General Foods, Inc. Bitterness inhibitors
HUT68764A (en) * 1991-11-27 1995-07-28 Bioresearch Inc Eatable taste modifiers
US5998641A (en) * 1997-01-31 1999-12-07 Unilever Patent Holdings Debittering of olive oil
US6022576A (en) * 1997-10-28 2000-02-08 Lipton, Division Of Conopco, Inc. Flavoring materials for use in tea containing beverages
US6036986A (en) * 1997-10-28 2000-03-14 Lipton, Division Of Conopco, Inc. Cinnamic acid for use in tea containing beverages
TR200001149T2 (en) * 1997-10-28 2000-08-21 Unilever N.V. A beverage that does not deteriorate in quality and is based on tea at room temperature.
EP1109461B1 (en) * 1998-07-07 2004-10-06 McNEIL-PPC, INC. Method of improving sweetness delivery of sucralose
US6991812B2 (en) * 2000-09-05 2006-01-31 Kao Corporation Agent for preventing, improving or treating hypertension
US7883856B2 (en) * 2001-04-05 2011-02-08 Senomyx Inc. Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators
JP3592681B2 (en) * 2001-05-16 2004-11-24 花王株式会社 Packaged beverage
JP3403400B1 (en) * 2001-09-28 2003-05-06 花王株式会社 Packaged beverage
JP3378577B1 (en) * 2001-09-28 2003-02-17 花王株式会社 Drink
ES2338562T3 (en) * 2003-12-18 2010-05-10 Kao Corporation BOTTLED DRINK.
JP2005312382A (en) * 2004-04-30 2005-11-10 Kakegawashi Nogyo Kyodo Kumiai Powdered tea containing catechin derived from natural tea leaf
DE102004041496A1 (en) * 2004-08-27 2006-03-02 Symrise Gmbh & Co. Kg Hydroxybenzoic acid amides and their use for masking bitter taste
JP2008537473A (en) * 2005-02-08 2008-09-18 セノミクス・インコーポレーテッド Acetaminophen, ranitidine, strychnine and denatonium p-human T2R receptors, and related assays for identifying human bitterness regulators
US20070059421A1 (en) * 2005-09-13 2007-03-15 Catani Steven J Methods and compositions to improve the palatability of foods
JP5140284B2 (en) * 2006-05-16 2013-02-06 花王株式会社 Container drink

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2010026003A1 *

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EP2323502B1 (en) 2012-09-05
EA018270B1 (en) 2013-06-28
WO2010026003A1 (en) 2010-03-11
CN102131404A (en) 2011-07-20
CN102131404B (en) 2013-07-24
US20100062131A1 (en) 2010-03-11
JP5730766B2 (en) 2015-06-10

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